Soft tissue sarcomas (STS) are a rare form of malignant tumors that arise from mesenchymal tissues and are primarily treated through surgical resection and radiation. For these procedures, a positive surgical margin is the greatest predictor of local recurrence, however, margin statuses following an STS resection is often determined weeks after the surgical procedure and can suffer from sampling error. This process is time consuming, delays patient care, and indicates the need for a rapid and accurate tool that can provide surgeons with immediate feedback during an operation. The ultimate goal of this proposal is to address that need and develop an optical system for intraoperative assessment of the tumor bed during STS excision. To that end, this study seeks to test the hypothesis that near-infrared autofluorescence imaging in combination with Raman spectroscopy can provide differential diagnoses of STS and surrounding tissues with high sensitivity and specificity. Three specific aims are proposed: (1) characterize the optical signatures of STS and surrounding tissues in vivo, (2) correlate the spectral markers of STS to the biochemical and structural basis of tissue pathogenesis, and (3) develop and test an optical device to evaluate the surgical margin of a large surface area within the tumor bed. Successful development of such a methodology will allow for in vivo detection of STS within the tumor bed and surrounding tissues, and could reduce the incidence of inadequate tumor excision during surgery. The method would prevent the need for multiple surgeries, reduce the patients' risk of surgical complications, and drastically reduce healthcare costs for this expanding patient population. In addition, the biochemical basis for STS pathogenesis and its effect on optical fluorescence will be explored.